Few Serious Infections Found Among Babies Exposed to Non-TNF Inhibitors

Evelyne Vinet, MD, PhD

Results of a recent study are suggesting children exposed to TNF inhibitors or tofacitinib in utero are at a low risk of experiencing serious infections as a result of the exposure.

Presented by Evelyne Vinet, MD, PhD, associate professor at McGill University in Montreal, at the 2019 American College of Rheumatology annual meeting, the analysis examined more than 15,000 children of mothers receiving TNF inhibitors or tofacitinib and found serious infections in just 1.9% of cases.

“This is a first step, as we need more data to confirm safety, particularly regarding other pregnancy outcomes,” Vinet said. “It is imperative that we further study this issue to provide firm evidence to guide treatment decisions prior to conception and throughout pregnancy.”

With pregnant women excluded from clinical trials and a persistent lack of real-world data a growing problem, investigators sought to evaluate the potential risk to offspring exposed to TNF inhibitor biologics and tofacitinib. To do so, investigators performed a cohort study that included 16,490 offspring of mothers receiving either therapy and 164,553 children born to unaffected matched mothers. Of the mothers included in the trial receiving non-TNFi biologics or tofacitinib, 4142 had rheumatoid arthritis, 381 had ankylosing spondylitis, 5743 had psoriatic osteoarthritis or psoriatic arthritis, and 6731 had inflammatory bowel disease.

For inclusion in the study mothers needed to be continuously enrolled within MarketScan for an year or more prior to delivery. Additionally, serious infections were defined as 1 or more hospitalization with infection as a primary diagnosis within the first year of life.

In regard to exposure to these agents, 105 children were exposed to tofacitinib or non-TNFi biologics while 1611 were exposed to TNFi during pregnancy. Of the 105 children, 4 were exposed to tofacitinib, 33 to abatacept, 4 to rituximab, 12 to tocilizumab, 42 to ustekinumab, and 10 to vedolizumab.

Upon analyses, 2 cases of serious infections among children exposed to tofacitinib or non-TNFi biologics were identified by study investigators(1.9%; 95% CI 0.3, 7.4). Of these 2 cases, one child was exposed to tofacitinib and the other to abatacept.

Investigators noted the percent of serious infections among children born to mothers with inflammatory diseases with no exposure to TNFi was 2.1% (95% CI 1.9, 2.3) while that rate was 2.3% (95% CI 1.6, 3.0) for those with TNFi exposure in utero. Investigators pointed out the percent5 of serious infection among unaffected mothers was 1.6% (95% CI 1.6, 1.7).

While there were few serious infections in their cohort study, which Vinet claimed used the largest cohort of pregnant women with chronic inflammatory disease ever assembled, investigators call for additional studies to examine the specific effects on individual therapies.

“In summary, in our large cohort, we detected very few cases of serious infection in children exposed to non-TNF inhibitors or tofacitinib and this will help guide clinicians who consult and mange women with chronic inflammatory disease,” Vinet said.

This study, titled “Babies Exposed to TNF Inhibitors or Tofacitinib in Utero Experience Very Few Serious Infections,” was presented at ACR 2019 by Evelyne Vinet, MD, PhD.